DOCSLIB.ORG

Bioactive Molecules from Amphibian Skin: Their Biological Activities with Reference to Therapeutic Potentials for Possible Drug Development

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Bioactive Molecules from Amphibian Skin: Their Biological Activities with Reference to Therapeutic Potentials for Possible Drug Development Indian Journal of Experimental Biology Vol. 45, July 2007, pp. 579-593 Review Article Bioactive molecules from amphibian skin: Their biological activities with reference to therapeutic potentials for possible drug development Antony Gomes1, Biplab Giri1, Archita Saha1, R Mishra1, Subir C Dasgupta1, A Debnath2 & Aparna Gomes2 1Laboratory of Toxinology and Experimental Pharmacodynamics Department of Physiology, University of Calcutta 92 A. P. C. Road, Kolkata 700 009, India 2Division of New Drug Development, Indian Institute of Chemical Biology 4 S. C. Mullick Road, Kolkata 700 032, India The amphibian skin contains various bioactive molecules (peptides, proteins, steroids, alkaloids, opiods) that possess potent therapeutic activities like antibacterial, antifungal, antiprotozoal, antidiabetic, antineoplastic, analgesic and sleep inducing properties. Research on amphibian skin derived biomolecules can provide potential clue towards newer drug development to combat various pathophysiological conditions. An overview on the bioactive molecules of various amphibian skins has been discussed. Keywords: Amphibians, Frog skin, Medicinal application, Skin bioactive molecules, Therapeutic potential, Toad skin The amphibians are defenseless creatures that are in traditional medicines. Torched newts are consumed preferably by a great variety of predators. sometimes sold in Asia as aphrodisiacs and the skin of In order to protect themselves from the potential certain species are said to cure illnesses. Superstitions predators, the amphibians have evolved different and folklore as these may be, they were actually the morphological, physiological and behavioral features. stepping-stones to modern biological sciences. One such defense mechanism is the slimy glandular In fact, toad and frog skin extracts have been used secretion by the skin. Frogs and toads have two types in Chinese medicine for treating various ailments. of skin glands–the mucous and the granular. The Chan Su is a traditional Chinese medicine prepared mucous glands occur throughout the skin and their from dried white secretion of the skin glands of secretion provides a moist coating that is necessary Chinese toad and has been used as an oriental drug for for cutaneous respiration. The granular glands, also treating heart diseases, toothache, sinusitis, called the serous or poison glands, may be distributed haemorrhage of gums and other systemic illnesses. across the body but are often concentrated around the Chinese doctors prescribed drinking of wine (in which head or neck, and are usually activated by stress or toad skin has been soaked) for the treatment of injury, and their secretions vary from species to leukemia. A well known, but somewhat toxic patent species from being slightly noxious to extraordinarily medicine, Liu Shen Wan (containing toad secretion toxic1. and realgar), is sometimes recommended by Chinese In many ancient cultures, amphibians are believed doctors for leukemia. Scientific research has to possess medicinal properties. Frog potions are used confirmed the presence of bufalin in Chan Su, which as aphrodisiacs, impotence and infertility preventions, is responsible for digoxin-like action2. Scientists have contraceptives and in many other illnesses. Also, also found that Chan Su possesses antineoplastic newts are often burned to ashes and then used in properties3 and components of Chan Su are capable of medicinal formulas and concoctions. Even today, the potentiating immune responses in experimental skins, bodies and body parts of salamanders are used animals4. Scientists throughout the world are now exploring the therapeutic potential of various toad and _______________ frog skin extracts and secretions. India, being a Phone: +91-33-2350-8386 (Extn 229); Fax: +91-33-2351-9755; +91-33-2241-3288 tropical country with diverse geographical variations, E-mail: [email protected] is home to wide species of toads, frogs and newts. 580 INDIAN J EXP BIOL, JULY 2007 There are about 200 species of frogs and toads in Na-K-ATPase activity12-17. The secretion from Bufo India. However, not much work has been carried out viridis Laur. skin glands produces a marked on toads and frog skin secretions in India as compared cardiotonic and vasotonic effect, increasing the to the rest of the world. Though, the jacket (coat) of intraventricular and aortal pressure, the rate of some of the most toxic frogs and toads might just be pressure growth in the ventricles and the contraction the treasure house, storing some of the best index of the myocardium on experimental dogs under pharmaceutical promises. The present communication anaesthesia18. is an effort to enlighten the importance of amphibian Antidiabetic activity skin – a future treasure house for development of Many insulinotropic peptides have been isolated novel drugs against several pathophysiological from different toad and frog skins. Insulin-releasing conditions. peptides (peaks 21, 22, 23, 24, 25) purified by reverse Cardiotonic and anti-arrhythmic activity phase HPLC from skin secretions of the toad Chan Su is prepared from skin secretion of Chinese Bombina variegata have molecular masses of 1.64, toad (Bufo bufo gargarizans), for treating arrhythmia 1.66, 1.68, 1.65 and 2.30 kDa, respectively19. They and other heart diseases. It had been introduced in significantly increase the insulin release by glucose Europe in 17th century and was later replaced by responsive BRIN-BD11 cells as compared to glucose digitalis some 200 years ago5. Kyushin (Japanese (5.6mM) alone. Peaks 21, 22 and 23 have sequence medicine similar to Chan Su) shows a beneficial homology to bombesin (Pyr-QRLGNQWAVGHLM) effect on congestive heart failure models in rabbits originally isolated from Bombina bombina, while due to its cardiotonic property6,7. The vasodilating peaks 24 and 25 are new. The mechanism underlying effect and positive inotropic action of Kyushin is their insulinotropic actions suggests possible probably due to beta-adrenergic action8. Kyushin involvement of a cAMP dependent G-protein significantly inhibits the aconitine-induced and insensitive pathway19. Fractions purified from skin thyroxine-induced arrhythmia in guinea pigs. The secretion of Rana palustris by reverse-phase HPLC decrease in heart rate induced by electrical stimulation also increased the insulin-releasing activity of BRIN- to the parasympathetic nerve (vagus nerve) can be BD11 cells. One such peptide (2.87 kDa) has a 27 restored by Kyushin, though Kyushin itself does not amino acid sequence, ALSILRGLEKLAKMGIAL- affect the conduction system in Langendorff TNCKATKKC (having 48% homology with preparation of rabbit hearts9. Kyushin dose- antimicrobial peptide Brevinin-120. Insulinotropic dependently increases the left ventricular pressure and peptides are also present in the skin secretions of mean aortic pressure and decreases the left ventricular Phyllomedusa trinitatis frog. One of them−a 28- end-diastolic pressure in a dose-dependent manner, amino-acid peptide had 100% homology with the C- but the myocardial oxygen consumption and heart rate terminal of the 75-amino-acid dermaseptin BIV are not significantly affected in anaesthetized dogs10. precursor in the skin of the Phyllomedusinae Bufalin and cinobufagin are the main components of subfamily21. Insulinotropic peptides were also Chan Su, which are responsible for its digitalis-like secreted by the skin of Agalychnis litodryas22 and action. Although Kyushin itself does not affect the Agalychnis calcarifer frogs23. An insulin-releasing conduction system, bufalin (0.3mg/ml) and peptide isolated from Rana pipiens had 100% cinobufagin (1 mg/ml) inhibit conduction in sequence homology with an antimicrobial peptide Langendorff preparation of isolated rabbit heart9. pipinin-124. Skin secretions of Rana saharica Bufalin, cinobufagin and some other bufadienolides possessed nontoxic insulinotropic peptides25. Two like bufotalin, cinobufotalin, gamabufotalin and were novel 1.89 and 2.93 kDa peptides. Other four resibufogenin⎯all show the cardiotonic effect in a (2.67, 3.51, 4.92 and 4.8 kDa) were identical to concentration-dependent manner in guinea pig brevinin-1E, brevinin-2EC, esculentin-1 and isolated heart preparations and cinobufagin possesses esculentin-1B, which belong to the group of the most cardiotonic action, similar to digitoxin, in antimicrobial peptides isolated from skin secretions of experimentally induced heart failure due to acute various Rana frog species. Contrast to the peptides local ischemia11. The cardiotonic steroids derived from Bombina, the mechanism underlying the from toad venom (bufalin, bufotalin, resibufagenin, insulinotropic actions of esculentins-1 and -1B marinobufagenin, marinoic acid, marinosin) all inhibit possibly involves both cyclic AMP-protein kinase A GOMES et al.: THERAPEUTIC POTENTIAL OF AMPHIBIAN SKIN BIOACTIVE MOLECULES 581 and C dependent G-protein sensitive pathways 26. from the skin secretions of the dusky gopher frog However, all the studies reported were done in vitro. (Rana sevosa), shares 77.8% homology with pLR, can It would be interesting to see if such compounds release histamine from rat peritoneal mast cells and could increase the insulin release in vivo. These inhibits the early development of granulocyte insulinotropic peptides may be exploited as macrophage colonies from bone marrow stem cells antidiabetic agents in the long run. but does not induce apoptosis of the end stage granulocytes31. Immunomodulatory activity The water-soluble, non-dialyzable
Load more

Recommended publications
  • Bufadienolides from the Skin Secretions of the Neotropical Toad Rhinella Alata (Anura: Bufonidae): Antiprotozoal Activity Against Trypanosoma Cruzi
    molecules Article Bufadienolides from the Skin Secretions of the Neotropical Toad Rhinella alata (Anura: Bufonidae): Antiprotozoal Activity against Trypanosoma cruzi Candelario Rodriguez 1,2,3 , Roberto Ibáñez 4 , Luis Mojica 5, Michelle Ng 6, Carmenza Spadafora 6 , Armando A. Durant-Archibold 1,3,* and Marcelino Gutiérrez 1,* 1 Centro de Biodiversidad y Descubrimiento de Drogas, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Apartado 0843-01103, Panama; [email protected] 2 Department of Biotechnology, Acharya Nagarjuna University, Nagarjuna Nagar, Guntur 522510, India 3 Departamento de Bioquímica, Facultad de Ciencias Naturales, Exactas y Tecnología, Universidad de Panamá, Apartado 0824-03366, Panama 4 Smithsonian Tropical Research Institute (STRI), Balboa, Ancon P.O. Box 0843-03092, Panama; [email protected] 5 Centro Nacional de Metrología de Panamá (CENAMEP AIP), Apartado 0843-01353, Panama; [email protected] 6 Centro de Biología Celular y Molecular de Enfermedades, INDICASAT AIP, Apartado 0843-01103, Panama; [email protected] (M.N.); [email protected] (C.S.) * Correspondence: [email protected] (A.A.D.-A.); [email protected] (M.G.) Abstract: Toads in the family Bufonidae contain bufadienolides in their venom, which are charac- Citation: Rodriguez, C.; Ibáñez, R.; terized by their chemical diversity and high pharmacological potential. American trypanosomiasis Mojica, L.; Ng, M.; Spadafora, C.; is a neglected disease that affects an estimated 8 million people in tropical and subtropical coun- Durant-Archibold, A.A.; Gutiérrez, M. tries. In this research, we investigated the chemical composition and antitrypanosomal activity Bufadienolides from the Skin of toad venom from Rhinella alata collected in Panama.
    [Show full text]
  • Preventive and Therapeutic Effects of Chinese Herbal Compounds Against Hepatocellular Carcinoma
    molecules Review Preventive and Therapeutic Effects of Chinese Herbal Compounds against Hepatocellular Carcinoma Bing Hu 1,*, Hong-Mei An 2, Shuang-Shuang Wang 1, Jin-Jun Chen 3 and Ling Xu 1 1 Department of Oncology and Institute of Traditional Chinese Medicine in Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; [email protected] (S.-S.W.); [email protected] (L.X.) 2 Department of Science & Technology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 202032, China; [email protected] 3 Department of Plastic & Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, The Ninth People’s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, China; [email protected] * Correspondence: [email protected]; Tel.: +86-21-64385700 Academic Editor: Derek J. McPhee Received: 16 November 2015 ; Accepted: 20 January 2016 ; Published: 27 January 2016 Abstract: Traditional Chinese Medicines, unique biomedical and pharmaceutical resources, have been widely used for hepatocellular carcinoma (HCC) prevention and treatment. Accumulated Chinese herb-derived compounds with significant anti-cancer effects against HCC have been identified. Chinese herbal compounds are effective in preventing carcinogenesis, inhibiting cell proliferation, arresting cell cycle, inducing apoptosis, autophagy, cell senescence and anoikis, inhibiting epithelial-mesenchymal transition, metastasis and angiogenesis, regulating immune function, reversing drug
    [Show full text]
  • Variety of Antimicrobial Peptides in the Bombina Maxima Toad and Evidence of Their Rapid Diversification
    http://www.paper.edu.cn 1220 Wen-Hui Lee et al. Eur. J. Immunol. 2005. 35: 1220–1229 Variety of antimicrobial peptides in the Bombina maxima toad and evidence of their rapid diversification Wen-Hui Lee1, Yan Li2,3, Ren Lai1, Sha Li2,4, Yun Zhang1 and Wen Wang2 1 Department of Animal Toxinology, Kunming Institute of Zoology, The Chinese Academy of Sciences (CAS), Kunming, P. R. China 2 CAS-Max Planck Junior Scientist Group, Key Laboratory of Cellular and Molecular Evolution, Kunming Institute of Zoology, The Chinese Academy of Sciences (CAS), Kunming, P. R. China 3 Graduate School of the Chinese Academy of Sciences, Beijing, P. R. China 4 Department of Pathology, University of Chicago, Chicago, USA Antimicrobial peptides secreted by the skin of many amphibians play an important role Received 30/8/04 in innate immunity. From two skin cDNA libraries of two individuals of the Chinese red Revised 4/2/05 belly toad (Bombina maxima), we identified 56 different antimicrobial peptide cDNA Accepted 14/2/05 sequences, each of which encodes a precursor peptide that can give rise to two kinds of [DOI 10.1002/eji.200425615] antimicrobial peptides, maximin and maximin H. Among these cDNA, we found that the mean number of nucleotide substitution per non-synonymous site in both the maximin and maximin H domains significantly exceed the mean number of nucleotide substitution per synonymous site, whereas the same pattern was not observed in other structural regions, such as the signal and propiece peptide regions, suggesting that these antimicrobial peptide genes have been experiencing rapid diversification driven by Darwinian selection.
    [Show full text]
  • The Journey of Life of the Tiger-Striped Leaf Frog Callimedusa Tomopterna (Cope, 1868): Notes of Sexual Behaviour, Nesting and Reproduction in the Brazilian Amazon
    Herpetology Notes, volume 11: 531-538 (2018) (published online on 25 July 2018) The journey of life of the Tiger-striped Leaf Frog Callimedusa tomopterna (Cope, 1868): Notes of sexual behaviour, nesting and reproduction in the Brazilian Amazon Thainá Najar1,2 and Lucas Ferrante2,3,* The Tiger-striped Leaf Frog Callimedusa tomopterna 2000; Venâncio & Melo-Sampaio, 2010; Downie et al, belongs to the family Phyllomedusidae, which is 2013; Dias et al. 2017). constituted by 63 described species distributed in In 1975, Lescure described the nests and development eight genera, Agalychnis, Callimedusa, Cruziohyla, of tadpoles to C. tomopterna, based only on spawns that Hylomantis, Phasmahyla, Phrynomedusa, he had found around the permanent ponds in the French Phyllomedusa, and Pithecopus (Duellman, 2016; Guiana. However, the author mentions a variation in the Frost, 2017). The reproductive aspects reported for the number of eggs for some spawns and the use of more than species of this family are marked by the uniqueness of one leaf for confection in some nests (Lescure, 1975). egg deposition, placed on green leaves hanging under The nests described by Lescure in 1975 are probably standing water, where the tadpoles will complete their from Phyllomedusa vailantii as reported by Lescure et development (Haddad & Sazima, 1992; Pombal & al. (1995). The number of eggs in the spawns reported Haddad, 1992; Haddad & Prado, 2005). However, by Lescure (1975) diverge from that described by other exist exceptions, some species in the genus Cruziohyla, authors such as Neckel-Oliveira & Wachlevski, (2004) Phasmahylas and Prhynomedusa, besides the species and Lima et al. (2012). In addition, the use of more than of the genus Agalychnis and Pithecopus of clade one leaf for confection in the nest mentioned by Lescure megacephalus that lay their eggs in lotic environments (1975), are characteristic of other species belonging to (Haddad & Prado, 2005; Faivovich et al.
    [Show full text]
  • Cinobufagin Inhibits Tumor Growth by Inducing Apoptosis Through Notch Signaling Pathways in Human Cholangiocarcinoma
    2469 Original Article Cinobufagin inhibits tumor growth by inducing apoptosis through Notch signaling pathways in human cholangiocarcinoma Jiajun Ren1, Shouhua Wang2, Longyang Jin2, Fei Ma3, Di Zhou2, Qiang Cai1 1Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; 2Department of General Surgery, 3Department of Oncology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China Contributions: (I) Conception and design: J Ren, D Zhou, Q Cai; (II) Administrative support: D Zhou, Q Cai; (III) Provision of study materials or patients: S Wang, L Jin; (IV) Collection and assembly of data: S Wang, F Ma; (V) Data analysis and interpretation: L Jin, F Ma; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Qiang Cai. Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin No. 2 Road, Shanghai 200025, China. Email: [email protected]; Di Zhou. Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China. Email: [email protected]. Background: Many studies have shown that cinobufagin has antitumor effects against many cancers. The aim of this study was to assess the effects of cinobufagin on cholangiocarcinoma (CCA) cells. Methods: Colony formation assay, cell-counting kit-8 (CCK-8) assay, and tumor xenograft experiments were applied to investigate the function of cinobufagin on human CCA cells, in vitro and in vivo. Flow cytometric analysis was performed to validate the effects of cinobufagin on cell apoptosis.
    [Show full text]
  • Release Calls of Four Species of Phyllomedusidae (Amphibia, Anura)
    Herpetozoa 32: 77–81 (2019) DOI 10.3897/herpetozoa.32.e35729 Release calls of four species of Phyllomedusidae (Amphibia, Anura) Sarah Mângia1, Felipe Camurugi2, Elvis Almeida Pereira1,3, Priscila Carvalho1,4, David Lucas Röhr2, Henrique Folly1, Diego José Santana1 1 Mapinguari – Laboratório de Biogeografia e Sistemática de Anfíbios e Repteis, Universidade Federal de Mato Grosso do Sul, 79002-970, Campo Grande, MS, Brazil. 2 Programa de Pós-graduação em Ecologia, Universidade Federal do Rio Grande do Norte, Lagoa Nova, 59072-970, Natal, RN, Brazil. 3 Programa de Pós-graduação em Biologia Animal, Laboratório de Herpetologia, Universidade Federal Rural do Rio de Janeiro, 23890-000, Seropédica, RJ, Brazil. 4 Programa de Pós-Graduação em Biologia Animal, Universidade Estadual Paulista (UNESP), 15054-000, São José do Rio Preto, SP, Brazil. http://zoobank.org/16679B5D-5CC3-4EF1-B192-AB4DFD314C0B Corresponding author: Sarah Mângia ([email protected]) Academic editor: Günter Gollmann ♦ Received 8 January 2019 ♦ Accepted 6 April 2019 ♦ Published 15 May 2019 Abstract Anurans emit a variety of acoustic signals in different behavioral contexts during the breeding season. The release call is a signal produced by the frog when it is inappropriately clasped by another frog. In the family Phyllomedusidae, this call type is known only for Pithecophus ayeaye. Here we describe the release call of four species: Phyllomedusa bahiana, P. sauvagii, Pithecopus rohdei, and P. nordestinus, based on recordings in the field. The release calls of these four species consist of a multipulsed note. Smaller species of the Pithecopus genus (P. ayeaye, P. rohdei and P. nordestinus), presented shorter release calls (0.022–0.070 s), with high- er dominant frequency on average (1508.8–1651.8 Hz), when compared to the bigger Phyllomedusa (P.
    [Show full text]
  • This Article Appeared in a Journal Published by Elsevier. the Attached
    (This is a sample cover image for this issue. The actual cover is not yet available at this time.) This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier’s archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/copyright Author's personal copy Toxicon 60 (2012) 967–981 Contents lists available at SciVerse ScienceDirect Toxicon journal homepage: www.elsevier.com/locate/toxicon Antimicrobial peptides and alytesin are co-secreted from the venom of the Midwife toad, Alytes maurus (Alytidae, Anura): Implications for the evolution of frog skin defensive secretions Enrico König a,*, Mei Zhou b, Lei Wang b, Tianbao Chen b, Olaf R.P. Bininda-Emonds a, Chris Shaw b a AG Systematik und Evolutionsbiologie, IBU – Fakultät V, Carl von Ossietzky Universität Oldenburg, Carl von Ossietzky Strasse 9-11, 26129 Oldenburg, Germany b Natural Drug Discovery Group, School of Pharmacy, Medical Biology Center, Queen’s University, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK article info abstract Article history: The skin secretions of frogs and toads (Anura) have long been a known source of a vast Received 23 March 2012 abundance of bioactive substances.
    [Show full text]
  • Toxicology in Antiquity
    TOXICOLOGY IN ANTIQUITY Other published books in the History of Toxicology and Environmental Health series Wexler, History of Toxicology and Environmental Health: Toxicology in Antiquity, Volume I, May 2014, 978-0-12-800045-8 Wexler, History of Toxicology and Environmental Health: Toxicology in Antiquity, Volume II, September 2014, 978-0-12-801506-3 Wexler, Toxicology in the Middle Ages and Renaissance, March 2017, 978-0-12-809554-6 Bobst, History of Risk Assessment in Toxicology, October 2017, 978-0-12-809532-4 Balls, et al., The History of Alternative Test Methods in Toxicology, October 2018, 978-0-12-813697-3 TOXICOLOGY IN ANTIQUITY SECOND EDITION Edited by PHILIP WEXLER Retired, National Library of Medicine’s (NLM) Toxicology and Environmental Health Information Program, Bethesda, MD, USA Academic Press is an imprint of Elsevier 125 London Wall, London EC2Y 5AS, United Kingdom 525 B Street, Suite 1650, San Diego, CA 92101, United States 50 Hampshire Street, 5th Floor, Cambridge, MA 02139, United States The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, United Kingdom Copyright r 2019 Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).
    [Show full text]
  • Rope Parasite” the Rope Parasite Parasites: Nearly Every AuSC Child I Ever Treated Proved to Carry a Significant Parasite Burden
    Au#sm: 2015 Dietrich Klinghardt MD, PhD Infec4ons and Infestaons Chronic Infecons, Infesta#ons and ASD Infec4ons affect us in 3 ways: 1. Immune reac,on against the microbes or their metabolic products Treatment: low dose immunotherapy (LDI, LDA, EPD) 2. Effects of their secreted endo- and exotoxins and metabolic waste Treatment: colon hydrotherapy, sauna, intes4nal binders (Enterosgel, MicroSilica, chlorella, zeolite), detoxificaon with herbs and medical drugs, ac4vaon of detox pathways by solving underlying blocKages (methylaon, etc.) 3. Compe,,on for our micronutrients Treatment: decrease microbial load, consider vitamin/mineral protocol Lyme, Toxins and Epigene#cs • In 2000 I examined 10 au4s4c children with no Known history of Lyme disease (age 3-10), with the IgeneX Western Blot test – aer successful treatment. 5 children were IgM posi4ve, 3 children IgG, 2 children were negave. That is 80% of the children had clinical Lyme disease, none the history of a 4cK bite! • Why is it taking so long for au4sm-literate prac44oners to embrace the fact, that many au4s4c children have contracted Lyme or several co-infec4ons in the womb from an oVen asymptomac mother? Why not become Lyme literate also? • Infec4ons can be treated without the use of an4bio4cs, using liposomal ozonated essen4al oils, herbs, ozone, Rife devices, PEMF, colloidal silver, regular s.c injecons of artesunate, the Klinghardt co-infec4on cocKtail and more. • Symptomac infec4ons and infestaons are almost always the result of a high body burden of glyphosate, mercury and aluminum - against the bacKdrop of epigene4c injuries (epimutaons) suffered in the womb or from our ancestors( trauma, vaccine adjuvants, worK place related lead, aluminum, herbicides etc., electromagne4c radiaon exposures etc.) • Most symptoms are caused by a confused upregulated immune system (molecular mimicry) Toxins from a toxic environment enter our system through damaged boundaries and membranes (gut barrier, blood brain barrier, damaged endothelium, etc.).
    [Show full text]
  • Pharmaceutical Sciences
    JOURNAL OF Pharmaceutical Sciences December 1967 volume 56, number 12 ___ Review Article __ Pharmacology and Toxicology of Toad Venom By K. K. CHEN and ALENA KOVARiKOVA CONTENTS speare made the witch throw a toad into the hell-broth. It has been long believed that han- HISTORY.. 1535 dling of toads causes warts. In a small area of CHEMICALINGREDIEXTSOF TOADPOISOX. 1536 Pharmacology of Bufadienolides. 1536 the state of Illinois, folklore has 300 references Bufagins. .... 1536 to warts of toad origin, particularly their cures (2). Bufotoxins. ... .. .. 1538 These superstitions can of course be disproved Clinical Trials... .... 1539 by laboratory experience. Houssay (3) op- Catecholamines. .. .. 1539 Epinephrine.. .. .. .. 1539 erated on 15,000 toads for endocrine studies and Norephinephrine.. .. .. .. .. 1539 we handled more than 10,000 toads for the Indolealkylamines..... 1539 collection of their poisons-with no ill effects. Noncardiotonic Sterols. .. 1540 In form of a votive animal, the toad is associated Cholesterol. ... .. .. ... .. .. 1540 with the uterus and various gynecological dis- Provitamin D. .. .. 1540 -v-Sitosterol .......... ... .. .. 1540 eases (4) in Central Europe. Bronze toads of Miscellaneous Substances.. 1540 the Perm culture of Kortheastern Russia were USE OF THE VENOMTO THE TOAD. 1540 among the archaeological findings dating from Protection from Enemies. 1540 the middle of the 1st century A.D. Significance to Behavior. 1540 ="ATURALTOLERANCETO CARDIACGLYCO- Toad medicine has been advocated all over SIDESANDAGLYCONES. 1540 the world. For many years the Chinese have RESPONSEOFOTHERTISSUESTODRUGS. 1541 used a preparation of toad venom, ch'an su, REFERENCES. 1541 for the treatment of canker sores, toothache, HISTORY sinusitis, and local inflammations (5). During the 15th century a European physician wrote a FOR CENTURIES the toad has been known to book, "De Vcnenis," in which he mentioned that produce a poisonous secretion.
    [Show full text]
  • Salmonella Typhimurium, the Major Causative Agent of Foodborne
    Salmonella Typhimurium, the major causative agent of foodborne illness inactivated by a phage lysis system provides effective protection against lethal challenge by induction of robust cell-mediated immune responses and activation of dendritic cells Gayeon Won, John Hwa Lee To cite this version: Gayeon Won, John Hwa Lee. Salmonella Typhimurium, the major causative agent of foodborne illness inactivated by a phage lysis system provides effective protection against lethal challenge by induction of robust cell-mediated immune responses and activation of dendritic cells. Veterinary Research, BioMed Central, 2017, 48 (1), pp.66. 10.1186/s13567-017-0474-x. hal-01623956 HAL Id: hal-01623956 https://hal.archives-ouvertes.fr/hal-01623956 Submitted on 25 Oct 2017 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Won and Lee Vet Res (2017) 48:66 DOI 10.1186/s13567-017-0474-x RESEARCH ARTICLE Open Access Salmonella Typhimurium, the major causative agent of foodborne illness inactivated by a phage lysis system provides efective protection against lethal challenge by induction of robust cell‑mediated immune responses and activation of dendritic cells Gayeon Won and John Hwa Lee* Abstract Salmonella Typhimurium infection via foodborne transmission remains a major public health threat even in devel- oped countries.
    [Show full text]
  • The Impact of Multiple Climatic and Geographic Factors on the Chemical Defences of Asian Toads (Bufo Gargarizans Cantor)
    www.nature.com/scientificreports OPEN The impact of multiple climatic and geographic factors on the chemical defences of Asian toads (Bufo gargarizans Cantor) Yueting Cao, Keke Cui, Hongye Pan, Jiheng Wu & Longhu Wang* Chemical defences are widespread in nature, yet we know little about whether and how climatic and geographic factors afect their evolution. In this study, we investigated the natural variation in the concentration and composition of the main bufogenin toxin in adult Asian toads (Bufo gargarizans Cantor) captured in twenty-two regions. Moreover, we explored the relative importance of eight climatic factors (average temperature, maximum temperature, minimum temperature, average relative humidity, 20–20 time precipitation, maximum continuous precipitation, maximum ground temperature, and minimum ground temperature) in regulating toxin production. We found that compared to toads captured from central and southwestern China, toads from eastern China secreted higher concentrations of cinobufagin (CBG) and resibufogenin (RBG) but lower concentrations of telocinobufagin (TBG) and cinobufotalin (CFL). All 8 climatic variables had signifcant efects on bufogenin production (ri>0.5), while the plastic response of bufogenin toxin to various climate factors was highly variable. The most important climatic driver of total bufogenin production was precipitation: the bufogenin concentration increased with increasing precipitation. This study indicated that the evolution of phenotypic plasticity in chemical defences may depend at least partly on the geographic variation of defensive toxins and their climatic context. Chemical defences is ubiquitous in nature and can serve for deterring predators, competitors, parasites, and path- ogens1–3. Many species can secrete a large diversity of toxic defensive compounds for self-protection.
    [Show full text]